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Biomedical subjects

J Butler

Publications and source records attributed to J Butler.

At least 199 records · Page 11Linked to original sources

Conformational structure of respiratory mucus studied by laser correlation spectroscopy.

Samples of respiratory mucus were obtained from the trachea of dogs and patients undergoing bronchoscopy. The samples were studied by laser correlation spectroscopy. The autocorrelation function of laser light scattered by both human and canine respiratory mucus was a single exponential in thick mucus or a double exponential in thin watery mucus. This finding suggests that, as in the case of uterine cervical mucus, the molecular structure of respiratory mucus is an ensemble of entangled, randomly-coiled glycoproteins forming a loose network of variable density rather than a covalently cross-linked molecular network as proposed in earlier studies.

Animals

Cigarette smoke and carbon monoxide do not have equivalent effects upon development of arteriosclerotic lesions.

Experiments were performed to test whether exposure to mainstream cigarette smoke, without any diet modification, was sufficient to exacerbate arteriosclerotic lesion development in cockerels. Additionally, the experiments were designed to test whether any such effect could be attributed solely to carbon monoxide (CO) in the smoke. Three groups of cockerels (7/group) were exposed 5 days/week in standard inhalation chambers. Each day, one group (smoke) was exposed to smoke produced from the combustion of two packs of cigarettes. A second group (CO) was exposed to CO at levels equivalent to those produced during the combustion of two packs of cigarettes. A third group was sham-exposed. Following sacrifice, the abdominal aorta of each animal was cut into 5 mm segments and the extent of arteriosclerotic lesion development was measured. In smoke animals, compared to those in either of the other two groups, there were more aortic segments with measurable lesions present and the cross-sectional areas of these segments were greater. On a comparative basis, the smoke lesions were three times larger than in either of the other two groups, despite the fact that blood carboxyhemoglobin levels were the same in CO and smoke animals. The location of the lesions and their histological appearance were very similar to those previously described for spontaneous and carcinogen-associated lesions in the cockerel. These results demonstrate that as little as four months of daily exposure to cigarette smoke, in the absence of a cholesterol supplemented diet, can help accelerate arteriosclerotic lesion development. Further, this accelerated development cannot be attributed solely to CO in the smoke.

Animals

Differentiation of muscle fiber types in aneurogenic brachial muscles of the chick embryo.

Cross-reinnervation studies performed ex ovo with newly hatched chicks demonstrate that peripheral motor neurons control the phenotypic characteristics of avian muscles. The present experiments were designed to determine whether or not nerves play a similar role during the initial expression of muscle fiber types. Previous experiments indicated that differentiation of specific fiber types occurs during the first week of embryogenesis, temporally coincident with the penetration of nerves within muscle masses. These observations suggested that peripheral nerves may be associated with the initial differentiation of fiber types. To test this hypothesis directly, anterior limb buds of the chick embryo were rendered aneurogenic by deletion of the brachial segment of the neural tube. To ensure a completely aneurogenic environment for developing brachial muscles, surgery was performed at day 2 in ovo before the exit of ventral root fibers. Experimental and control embryos from Stage (St) 25 (4.5 d) through St 45 (19d) were analyzed histochemically by a silver-cholinesterase reaction to detect nerves and by the myosin ATPase reaction, following alkali and acid preincubation, to determine the fiber type composition of the muscles. In addition, the total volume of aneurogenic and control muscles was compared. Results demonstrate that the characteristic myosin ATPase profiles of individual aneurogenic and innervated (control) muscles were identical throughout the entire period analyzed. Therefore, we conclude that these enzymic profiles are endogenously expressed and are not under neuronal control during early embryogenesis. Furthermore, the entire sequence of events from the migration of myogenic cells to the anterior limb bud through the division of the primary muscle masses to form individual brachial muscles proceeded on schedule in the absence of nerves. Since the growth of aneurogenic muscles was impaired, we conclude that during embryogenesis peripheral motor nerves are necessary initially for the proper growth of muscles and ultimately, for their survival. They are not involved, however, with either the initial formation or initial differentiation of individual brachial muscles.

Adenosine Triphosphatases

Kinetics and mechanism of the reduction of ferricytochrome c by the superoxide anion.

The temperature and pH dependence of the reaction of the superoxide radical anion with ferricytochrome c have been measured using the pulse-radiolysis technique. The temperature dependence of the reaction at low ionic strength yields an activation energy of 31 +/- 5 kJ/mol as compared to 14 +/- 3 kJ/mol for the reaction of CO2.(-) under the same conditions. The pH dependence fits the single pK'a of ferricytochrome c of 9.1. The bimolecular rate constant for the reaction of the superoxide anion with ferricytochrome c at pH 7.8, 21 +/- 2 degrees C, in the presence of 50 mM phosphate and 0.1 mM EDTA is (2.6 +/- 0.1) X 10(5) M-1 s-1. Using this value, 1 unit of superoxide dismutase activity (McCord, J. M., and Fridovich, I. (1969) J. Biol. Chem. 244, 6049-6055) is calculated to be 3.6 +/- 0.3 pmol of enzyme if the assay is performed in a total volume of 3.0 ml. Copper ions reduce the yield of the reaction of ferricytochrome c with CO2.(-). The reactivities of native and singly modified 4-carboxy-2,4-dinitrophenyllysine cytochromes c towards the superoxide anion radical are in the order native greater than 4-carboxy-2,4-dinitrophenyllysine 60 greater than lysine 13 greater than lysine 87 greater than lysine 27 greater than lysine 86 greater than lysine 72, indicating that electron transfer takes place at or close to the solvent accessible heme edge. The mechanism of the reaction is discussed in terms of the approach of superoxide anion radicals to the heme edge and the available molecular orbitals of both heme and free radicals.

Animals

Mechanism by which positive end-expiratory pressure increases cerebrospinal fluid pressure in dogs.

We investigated possible mechanisms by which positive end-expiratory pressure (PEEP) increased cerebrospinal fluid pressure (PCSF) in anesthetized mechanically ventilated dogs. In part I of the study, PEEP was applied in 5 cmH2O increments each lasting 1-2 min, before and after a snare separated the spinal from the cerebral subarachnoid space in each animal. Next, with the spinal cord still ligated, the dogs were ventilated without PEEP while superior vena cava pressure (PSVC) was raised in 5 cmH2O increments by means of a fluid reservoir connected with the superior vena cava. Cerebrospinal fluid pressure in the cisterna magna increased immediately and in parallel with PEEP before and after the spinal subarachnoid space was occluded and also increased when PSVC was raised independently; in all circumstances the increase in PCSF correlated closely with PSVC (r = 0.926). In part II of the study, arterial blood gases were drawn before and after PEEP was applied in the same increments and for the same duration as in part I. Cerebrospinal fluid pressure measured with a hollow skull screw again rose in parallel with PEEP, whereas arterial carbon dioxide tension rose only slightly at 60 s. In part III of the study, mean arterial pressure (Pa) was allowed to decrease with PEEP or was held constant by distal aortic obstruction and volume infusion. Cerebrospinal fluid pressure increased regardless of Pa, but the increase was greater when Pa was held constant than when it fell with PEEP. We conclude that PEEP increases PCSF primarily by increasing PSVC and decreasing cerebral venous outflow. This effect is augmented if cerebral arterial inflow is increased as well.

Animals

Estimation of transmural cardiac pressures during ventilation with PEEP.

Assessment of ventricular performance during positive end-expiratory pressure (PEEP) requires accurate measurement of transmural cardiac pressures. We investigated the influence of PEEP on the atrial and juxtacardiac pressures estimated by different methods in eight dogs. Left atrial pressure was measured by hydraulic and transducer-tipped catheter systems. Juxtacardiac pressure was estimated by an esophageal balloon and by air- and fluid-filled mediastinal wafer sensors. The supine canine heart was observed radiographically to lift and tilt during PEEP subjecting the left atrial catheters and the fluid-filled mediastinal wafer to a hydrostatic pressure increase. The esophageal balloon seriously underestimated the pressure increment occurring during the application of PEEP in the supine (but not prone) position, perhaps because mediastinal weight was lifted from the esophagus during lung distension. Similar phenomena were also observed in three human subjects. We conclude that lung distension lifts and tilts the heart in a supine preparation causing a hydrostatic increase of intracavitary pressure and attenuation of the esophageal pressure increment. These effects help to account for the apparent alterations of ventricular compliance and performance previously attributed to PEEP.

Animals

A Starling resistor regulates cerebral venous outflow in dogs.

This investigation was undertaken to determine whether a Starling resistor or venous waterfall effect exists between the sagittal sinus and the cerebral veins such that increases in sagittal sinus pressure (Pss) do not abolish cerebral venous outflow and to examine two possible contributions of extracranial venous valves in regulating outflow. Anesthetized dogs were subjected to positive end-expiratory pressure (PEEP) before and after intracranial pressure (Pic) was elevated by inflation of an epidural balloon. PEEP raised Pss equally in all animals, but Pic and cerebral venous pressure (Pcv) increased less in the presence of intracranial hypertension. When Pss was low, passage of a catheter in the cerebral vein in and out of the sagittal sinus demonstrated an abrupt drop in pressure as the sinus was entered. When Pss was raised and lowered independently of superior vena caval pressure (Psvc) the changes in Pic and Pcv were less when Pss was decreased than when it was increased. Sustained increases and decreases in Psvc caused increases and decreases in Pcv, Pic, Pss, and external jugular venous pressure (Pejv) regardless of whether external jugular venous valves were present or absent. We conclude that a Starling resistor between the sagittal sinus and the cerebral veins regulates cerebral venous outflow when Pss is increased by PEEP and other maneuvers that raise Psvc. The waterfall maintains Pcv and Pic at normal levels when Psvc and Pss are reduced. Extracranial venous valves are not essential to this mechanism.

Animals

Federal health program reforms: implications for child health care.

The "Omnibus Budget Reconciliation Act of 1981" included a number of provisions designed to reduce federal spending for health care and to increase state authority over health programs. Evidence concerning the financial condition and health care needs of children served by federally-financed health programs, and recent trends in coverage and eligibility, make it possible to assess the likely impact of the new legislation. One conclusion seems clear: extensive federal funding reductions cannot be accommodated by eliminating excesses. While reforms of the Medicaid program may be advisable for a number of reasons, a simple reduction to funding will have serious, adverse consequences for poor children.

Aid to Families with Dependent Children

A non-equilibrium state of deoxyhaemoglobin. Temperature-dependence and oxygen binding.

After reduction of human methaemoglobin by solvated electrons a non-equilibrium low-spin state of deoxyhaemoglobin is formed which has the characteristic haemochrome spectrum. This haemochrome state is ascribed to a weakly 6-coordinated structure of the haem, which is stabilised by the protonated distal histidine. Oxygen binding is not inhibited by the presence of the weak interaction in the haemochrome state. From the pH dependence of the biphasic behaviour of the oxygen binding a pK of about 8.8 is obtained which is ascribed to the deprotonation of the distal histidine which is in the proximity of a negative ion. A model is proposed to explain the complex spin-equilibria observed in methaemoglobin. The enthalpy of activation of the decay of the haemochrome state is about 53 kJ x mol(-1) and increases to 90 kJ x mol(-1) in the presence of 1 M methanol, indicating a strong interaction between methanol and haemoglobin. Around pH 8.4 the rate constant of the binding of oxygen to the haemochrome state is so high that it may well be diffusion controlled.

Chemical Phenomena

Kinetic data for redox reactions of cytochrome c with Fe(CN)5X complexes and the question of association prior to electron transfer.

Use of rigorous equilibration kinetics to evaluate rate constants for the Fe(CN)6 4- reduction of horse-heart cytochrome c in the oxidized form, cyt c (III), has shown that limiting kinetics do not apply with concentrations of Fe(CN)6 4- (the reactant in excess) in the range 2-10 x 10(-4) M, I = 0.10 M (NaCl). The reaction conforms to a first-order rate law in each reactant, and at 25 degrees C, pH 7.2 (Tris), it is concluded that K for association prior to electron transfer is less than 200 M-1. From previous studies at 25 degrees C, ph 7.0 (10(-1) M phosphate), I = 0.242 M (NaCl), a value K = 2.4 x 10(3) M-1 has been reported. Had such a value applied, some or all of the redox inactive complexes Mo(CN)8 4-, Co(CN)6 3-, Cr(CN)6 3-, Zr(C2O4)4 4- present in amounts 5-20 x 10(-4) M would have been expected to associate at the same site and partially block the redox process. No effect on rats was observed. With the reductants Fe(CN)5(4-NH2-py)3- and Fe(CN)5(imid)3-, reactions proceeded to greater than 90% completion and rate laws were again first order in each reactant. Rate constants (M-1 sec-1) at 25 degrees C, pH 7.2 (Tris), I = 0.10 M (NaCl), are Fe(CN)6 4- (3.5 x 10(4)), Fe(CN)5(4-NH2py)3- (6.7 x 10(5), and Fe(CN)5(imid)3- (4.2 x 10(5). Related reactions in which cyt c(II) is oxidized are also first order in each reactant, Fe(CN)6 3- (9.1 x 10(6)), Fe(CN)5(NCS)3- (1.3 x 10(6)), Fe(CN)5(4-NH2py)2- (3.8 x 10(6) at pH 9.4), and Fe(CN)5(NH3)2- (2.75 x 10(6) at ph 8). Redox inactive Co(CN)6 3- (1.0 x 10(-3) M) has no effect on the reaction of Fe(CN)6 3- which suggests that a recent interpretation for the Fe(CN)6 3- oxidation of cyt c(II), I = 0.07 M, may also require reappraisal.

Animals